Amniotic fluid of primates contains a high concentration of prolactin of decidual origin which decreases with intrauterine bacterial infection prior to preterm labor. Prostaglandins (PGs) and cytokines increase in amniotic fluid after infection in vivo and inhibit decidual prl secretion in vitro. To determine if PGs or cytokines mediate the effect of bacterial infection on prolactin in the whole animal, chronically instrumented pregnant rhesus monkeys were prepared. Interleukin (IL)-1 (10 fg; 6 ml/hr for 2 hr) was infused into the amniotic cavity alone (n=6), and during a longer term treatment with indomethacin (n=5). In animals which received both treatments serially (n-4), the infusion with indomethacin preceded the infusion of IL-1 alone because IL-1 can induce preterm labor. Amniotic fluid samples were obtained relative to infusion at -24 hr and -1 hr, then at least once during the following 24 hr, and again between 25 hr and 72 hr. Samples were frozen at -20xC until assay for prolactin. Amniotic fluid levels of IL-1 were verified and PGE2 and PGF2` were also measured. Prolactin levels were expressed as a percent of preinfusion values and compared with ANOVA followed by pairwise comparison. IL-1 levels greater than 10 ng/ml were achieved due to infusion. PGs were unchanged during indomethacin treatment, but increased significantly following IL-1 alone. Prior to IL-1 infusion, prolactin levels averaged 82 q 20 fg/ml. Infusion of IL-1 caused a significant 42% decrease in amniotic fluid prolactin by 24 hr (p<0.05 vs preinfusion) and a 66% decline by 72 hr (p<0.05 vs 24 hr). There was an increase in uterine activity at 6.0 q 2.4 hr after infusion. Infusion of indomethacin for 48 hr preceding IL-1 plus 72 hr following IL-1 did not abolish the effect of IL-1 on the decline of prolactin levels. Prolactin levels were 41% less than preinfusion values by 25-72 hr post-infusion (p<0.05) in the presence of indomethacin. Indomethacin did prevent the increase in uterine activity which was induced by IL-1 alone. In summary, IL-1 caused a decrease in amniotic fluid prolactin in a manner similar to bacterial infection. Blockade of PG production prevented uterine contractions, but it did not prevent the decline in amniotic fluid prolactin. These results support the notion that IL-1 may act directly on decidual cells and inhibit prolactin secretion.